Pancreatic cancer is the fourth most common cause of cancer deaths in the United States (U.S.), has a very poor prognosis, and is generally unresponsive to conventional therapies. Therefore, it is critical to identify modifiable factors that can be used in prevention efforts to reduce risk for developing this disease. Diet, physical activity, and obesity have been postulated to potentially influence pancreatic cancer risk, but results are inconsistent. Also, millions of Americans use dietary (vitamin, mineral, and herbal) supplements to prevent cancer and other diseases, but with few exceptions, there is sparse evidence for either their benefits or risks. Specific Aims The goal of this study is to examine associations of various dietary supplements with pancreatic cancer incidence, using previously collected data from a large cohort study with a high proportion of supplement users. The primary specific aims are to investigate associations of supplemental intakes of nutrients with anti-inflammatory (vitamin E, selenium, and omega-3 fatty acids) and antioxidant properties (vitamin C, vitamin E, beta-carotene, lycopene, and selenium) over the 10-year period ending at baseline with the incidence of pancreatic cancer. Secondary aims are to examine associations of intakes of specific, less common vitamin, mineral, botanical, and other supplements (e.g., folate, iron, gingko biloba) and non- steroidal anti-inflammatory drugs (NSAIDs);as well as physical activity and body mass index levels at baseline and ages 18, 30, and 45 years with pancreatic cancer incidence. Methods Between 2000-2002, 77,738 men and women, aged 50-76 from western Washington State completed a baseline questionnaire that captured detailed information on use of 38 supplements over the previous 10 years, diet, physical activity (using a validated questionnaire), anthropometrics, health history, and cancer risk factors. Supplement users were targeted in recruitment;therefore, supplement use by cohort members is both high and of long duration: 79% were ever users of a supplement, and 66% used multivitamins,46% used individual vitamin C, and 47% used individual vitamin E, typically for 5-8 of the previous 10years. The cohort is being followed for pancreatic cancers by linkage to the western Washington SEER cancer registry, deaths by linkage to the Washington State death file, and out-migration from the SEER catchment area by linkage to the National Change of Address system. This proposal seeks funds to conduct analyses addressing the specific aims. We expect to identify 215 pancreatic cancer cases after a mean follow-up of 8.3 years. The primary exposure would be average intake per day over the previous 10 years of the nutrient of interest (single supplements plus multivitamins), and all analyses will be adjusted for diet and other potential confounders and effect modifiers. Significance The results of this study will be one of the first to examine associations of dietary supplement use, as well as physical activity and obesity, with risk for pancreatic cancer, a disease with a high fatality rate and few known modifiable risk factors. We would use data from the only cohort study specifically focused on the etiologic relationships of dietary supplements with cancer risk which carefully measured supplement use and confounding factors. Importantly, given the high prevalence of dietary supplement use in the U.S., our findings will have important public health implications regardless of whether we find protective effects, increased risks, or no effects of supplements on pancreatic cancer risk. PUBLIC HEALTH RELEVANCE: Pancreatic cancer is a highly fatal disease for which there are few known modifiable risk factors. It has been suggested that diet, physical activity, and obesity may impact pancreatic cancer development, but results are inconsistent. Also, many Americans use dietary (vitamin, mineral, and herbal) supplements with limited knowledge regarding their potential benefits and risks. The goal of this proposed study is to examine associations of various dietary supplements, as well as physical activity and body mass index levels at baseline and ages 18, 30, and 45 years, with pancreatic cancer incidence. To accomplish these aims, we would conduct secondary data analyses within a large cohort of men and women (n=77,738), 50-76 years (at baseline) in western Washington state. Cohort members completed a detailed baseline questionnaire covering supplement use over the past 10 years, diet, physical activity, anthropometrics, health history, and cancer risk factors. An expected 215 pancreatic cancer cases would be identified after a mean follow-up of 8.3 years by linkage to the western Washington SEER cancer registry. This proposed project would provide valuable information regarding whether use of dietary supplements, as well as physical activity and body mass index are associated with pancreatic cancer incidence, and would be useful for the millions of American adults who take supplements, regardless of whether protective effects, no effects, or increased risks for specific supplements are found.